Signs Of Structural Damage Research Articles

TB DURING THE SEROCONVERSION PHASE

TB DURING THE SEROCONVERSION PHASE

An optimized protocol for single nuclei isolation from clinical biopsies for RNA-seq

Single nuclei RNA sequencing (snRNA-seq) has evolved as a powerful tool to study complex human diseases. Single cell resolution enables the study of novel cell types, biological processes, cell trajectories, and cell–cell signaling pathways. snRNA-seq largely relies on the dissociation of intact nuclei from human tissues. However, the study of complex tissues using small core biopsies presents many technical challenges. Here, an optimized protocol for single nuclei isolation is presented for frozen and RNAlater preserved human kidney biopsies. The described protocol is fast, low cost, and time effective due to the elimination of cell sorting and ultra-centrifugation. Samples can be processed in 90 min or less. This method is effective for obtaining normal nuclei morphology without signs of structural damage. Using snRNA-seq, 16 distinct kidney cell clusters were recovered from normal and peri-transplant acute kidney injury allograft samples, including immune cell clusters. Quality control measurements demonstrated that these optimizations eliminated cellular debris and allowed for a high yield of high-quality nuclei and RNA for library preparation and sequencing. Cellular disassociation did not induce cellular stress responses, which recapitulated transcriptional patterns associated with standardized methods of nuclei isolation. Future applications of this protocol will allow for thorough investigations of small biobank biopsies, identifying cell-specific injury pathways and driving the discovery of novel diagnostics and therapeutic targets.

Correlation of enthesial and synovial inflammation in patients with psoriatic arthritis: Data of clinical and ultrasonographic study

Objective. Assessment of clinical manifestations and ultrasonographic signs of enthesitis (En) in patients with psoriasis (PsO) and psoriatic arthritis (PsA).Subjects and methods. The study is based on the analysis of survey data from 106 patients with PsO for the period 2018–2021, which were firstly sent by dermatologists for a consultation with a rheumatologist due to musculoskeletal pain. The duration of the period of musculoskeletal pain in the observed patients did not exceed 12 months. In addition to general clinical and laboratory examination, all patients underwent ultrasonography of painful and/or swollen joints, tendons and ligaments using a linear sensor (frequency – 12–18 MHz) of MyLab 50 (Esaote, Italy) apparatus and supplemented by Doppler energy study with a pulse frequency of 6.6 MHz. The OMERACT definitions were used to identify En, synovitis and tenosynovitis.Results and discussion. The diagnosis of PsA was established in 73.6%, osteoarthritis – in 13.2%, gout – in 8.4%, fibromyalgia – in 17.9%. Ultrasonographic signs of En were found in 67.9% of patients: signs of an active inflammatory process in enthesises (decreased echogenicity, thickening and appearance of Doppler signals) were observed in 48.7%, signs of structural damage to enthesial zones (calcifications, enthesophytes and bone erosions) in 25,6% of patients. Isolated En was found in 24.4% of patients, a combination of En and synovitis – in 32.1% of patients, a combination of En and tenosynovitis – in 20.5% of patients. The correlation between the inflammatory domain values of the ultrasoundographic enthesial index MASEI (Madrid Sonographic Enthesitis Index) and the clinical enthesial index LEI (Leeds Enthesitis Index) was 0.71 [0.58; 0.77]. There were less pronounced clinical indicators of enthesial inflammation (lower LEI index values), functional disorders of the joints (lower values of the HAQ-DI index) and laboratory signs of systemic inflammation (lower CRP values) in patients with isolated En in comparison with combination of En and synovitis. Ultrasonographic signs of structural damage of enthesises were observed in 15.4% of patients without clinical and ultrasonographic signs of active En, which may indicate the possibility of a subclinical course of enthesial inflammation in patients with PsO.Conclusion. It was demonstrated that ultrasonography has diagnostic capabilities to identify the site of the inflammatory process in patients with PsA and differentiate patients with isolated En and a combination of En and synovitis in order to select a method of differentiated anti-inflammatory therapy.

Penetrating injury with an arrow impacted in the neck in rural Tanzania, a case report.

Introduction and importancePenetrating neck injuries refer to neck injuries that penetrate through the platysma layer which can cause life-threatening injuries to the aerodigestive and neurovascular systems. Currently penetrating neck injuries are mainly due to modern firearms however penetrating neck injuries due to arrows are still seen, although rare, in rural areas among developing countries. Management depends on hemodynamic stability, signs of structural damage and zone of neck involved.Case presentation19-year-old male presenting with a penetrating arrow impacted in his neck following an attack by cattle raiders who was otherwise stable of presentation. Underwent preoperative imaging with removal of the arrow under general anaesthesia via surgical exploration.Clinical discussionWe concur with the recommendation to first obtain adequate imaging to establish degree of injury as well as for operative planning. Removal of impacted arrow should not be carried out blindly but rather in a controlled environment under general anaesthesia via surgical exploration.ConclusionPenetrative arrow injuries to the neck are an archaic problem that can be dealt with via modern surgical principles towards penetrating neck injuries. Unstable patients warrant emergent exploration however stable patients can first be worked up appropriately to ascertain degree of injury. Impacted arrows can then be removed safely under general anaesthesia rather than risk further injury to critical structures via blind removal.

Veno-Venous Extracorporeal Membrane Oxygenation in Minipigs as a Robust Tool to Model Acute Kidney Injury: Technical Notes and Characteristics.

ObjectiveVeno-venous extracorporeal membrane oxygenation (vv-ECMO) can save lives in severe respiratory distress, but this innovative approach has serious side-effects and is accompanied by higher rates of iatrogenic morbidity. Our aims were, first, to establish a large animal model of vv-ECMO to study the pathomechanism of complications within a clinically relevant time frame and, second, to investigate renal reactions to increase the likelihood of identifying novel targets and to improve clinical outcomes of vv-ECMO-induced acute kidney injury (AKI).MethodsAnesthetized Vietnamese miniature pigs were used. After cannulation of the right jugular and femoral veins, vv-ECMO was started and maintained for 24 hrs. In Group 1 (n = 6) ECMO was followed by a further 6-hr post-ECMO period, while (n = 6) cannulation was performed without ECMO in the control group, with observation maintained for 30 h. Systemic hemodynamics, blood gas values and hour diuresis were monitored. Renal artery flow (RAF) was measured in the post-ECMO period with an ultrasonic flowmeter. At the end of the experiments, renal tissue samples were taken for histology to measure myeloperoxidase (MPO) and xanthine oxidoreductase (XOR) activity and to examine mitochondrial function with high-resolution respirometry (HRR, Oroboros, Austria). Plasma and urine samples were collected every 6 hrs to determine neutrophil gelatinase-associated lipocalin (NGAL) concentrations.ResultsDuring the post-ECMO period, RAF dropped (96.3 ± 21 vs. 223.6 ± 32 ml/min) and, similarly, hour diuresis was significantly lower as compared to the control group (3.25 ± 0.4 ml/h/kg vs. 4.83 ± 0.6 ml/h/kg). Renal histology demonstrated significant structural damage characteristic of ischemic injury in the tubular system. In the vv-ECMO group NGAL levels, rose significantly in both urine (4.24 ± 0.25 vs. 2.57 ± 0.26 ng/ml) and plasma samples (4.67 ± 0.1 vs. 3.22 ± 0.2 ng/ml), while tissue XOR (5.88 ± 0.8 vs. 2.57 ± 0.2 pmol/min/mg protein) and MPO (11.93 ± 2.5 vs. 4.34 ± 0.6 mU/mg protein) activity was elevated. HRR showed renal mitochondrial dysfunction, including a significant drop in complex-I-dependent oxidative capacity (174.93 ± 12.7 vs. 249 ± 30.07 pmol/s/ml).ConclusionSignificantly decreased renal function with signs of structural damage and impaired mitochondrial function developed in the vv-ECMO group. The vv-ECMO-induced acute renal impairment in this 30-hr research protocol provides a good basis to study the pathomechanism, biomarker combinations or possible therapeutic possibilities for AKI.

Experimental-numerical studies on the first-ply failure analysis of real, thin walled laminated angle columns subjected to uniform shortening

This study investigates the behaviour of real short thin-walled laminated angle columns subjected to uniform shortening. Numerical analyses and experiments were conducted over the full range of loading until the initiation of structural damage. The experiments were performed on a universal testing machine with the use of the Aramis digital image correlation system for displacement/strain measurement. The first signs of structural damage were detected by acoustic emission method. The numerical analysis was performed by the finite element method using Abaqus software. Different failure criteria were considered in the numerical analysis, including the Tsai-Wu criterion, Tsai-Hill criterion, Azzi-Tsai-Hill criterion, maximum stress criterion and Hashin criterion. The numerical analysis also investigated the effect of elastic pads that were used in the experiments to reduce the impact of local effects and geometric imperfection of column ends. Obtained numerical and experimental results show very good agreement.

Direct contact ultrasound for fouling control and flux enhancement in air-gap membrane distillation.

Air Gap Membrane distillation (AGMD) is a thermally driven separation process capable of treating challenging water types, but its low productivity is a major drawback. Membrane fouling is a common problem in many membrane treatment systems, which exacerbates AGMD's low overall productivity. In this study, we investigated the direct application of low-power ultrasound (8-23 W), as an in-line cleaning and performance boosting technique for AGMD. Two different highly saline feedwaters, namely natural groundwater (3970 μS/cm) and RO reject stream water (12760 μS/cm) were treated using Polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF) membranes. Theoretical calculations and experimental investigations are presented, showing that the applied ultrasonic power range only produced acoustic streaming effects that enhanced cleaning and mass transfer. Attenuated Total Reflection Fourier-Transform Infrared Spectroscopy (ATR FT-IR) analysis showed that ultrasound was capable of effectively removing silica and calcium scaling. Ultrasound application on a fouled membrane resulted in a 100% increase in the permeate flux. Cleaning effects accounted for around 30-50% of this increase and the remainder was attributed to mass transfer improvements. Contaminant rejection percentages were consistently high for all treatments (>99%), indicating that ultrasound did not deteriorate the membrane structure. Scanning Electron Microscopy (SEM) analysis of the membrane surface was used to confirm this observation. The images of the membrane surface demonstrated that ultrasound successfully cleaned the previously fouled membrane, with no signs of structural damage. The results of this study highlight the efficient and effective application of direct low power ultrasound for improving AGMD performance.

Molecular imaging of neuroinflammation in patients after mild traumatic brain injury: a longitudinal 123 I-CLINDE single photon emission computed tomography study.

Neuroinflammation has been proposedas part ofthe pathogenesis of post-concussionsymptoms (PCS), but the inflammatory response of the human brain to mildtraumatic brain injury (mTBI) remains unknown. We hypothesized that a neuroinflammatory responseis present in mTBI at 1-2weeks post-injury and persists in patients with PCS. We scanned 14 patients with mTBI without signs of structural damage at 1-2weeks and 3-4months post-injury and 22 healthy controlsonceusing the single photon emission computed tomography tracer 123 I-CLINDE, which visualizes translocator protein(TSPO), aprotein upregulated in active immune cells. PCS was defined as three or more persisting symptoms from theRivermead Post Concussion SymptomsQuestionnaireat 3monthspost-injury. Across brain regions, patients had significantly higher 123 I-CLINDE binding to TSPO than healthy controls, both at 1-2weeks after the injury in all patients (P=0.011) and at 3-4months in the seven patients with PCS (P=0.006) and in the six patients with good recovery (P=0.018). When the nine brain regions were tested separately and results were corrected for multiple comparisons, no individual region differed significantly, but all estimated parameters indicated increased 123 I-CLINDEbinding to TSPO,ranging from 2% to 19% in all patients at 1-2weeks, 13% to 27% in patients with PCS at 3-4months and -9% to 17% in patients with good recovery at 3-4months. Neuroinflammationwas presentinmTBI at1-2weeks post-injury and persisted at 3-4months post-injury with a tendency to be most pronounced in patients with PCS.

Is all chronic kidney disease created equal?

Chronic kidney disease (CKD) has generally been characterized functionally as a glomerular filtration rate (GFR) less than 60 ml/min/1.73 m², without accounting for cause, signs of structural damage, or relative risk of sequelae. Recently released guidelines define CKD as abnormalities of kidney structure or function, present for more than 3 months. We review the recent literature about CKD and its implications for renal surgery. Most estimates of GFR are based on serum creatinine, after adjusting for age, race, sex, and/or body mass. Recent research indicates that many individuals have GFR values less than 60 ml/min/1.73 m² without other manifestations of CKD. Nephron loss due to normal aging or renal surgery (CKD-S) may have lower likelihood of CKD progression, and may infer better survival, compared to individuals with the same degree of CKD due to medical causes. Patients with mild and moderate CKD due to surgical nephron loss may benefit from an alternative measurement method of renal function such as cystatin-C-derived or directly measured GFR. CKD includes a diverse group of individuals with reduced GFR from a variety of causes. Classification of CKD according to GFR, albuminuria, and cause, may improve the management of patients with reduced GFR, as some causes (e.g., nephrectomy and aging) appear to be associated with a relatively low risk of progression.

Hydrodissection for improved microsurgical denervation of the spermatic cord: prospective blinded randomized control trial in a rat model

Microsurgical denervation of the spermatic cord (MDSC) may provide a 70-85% success rate in eliminating pain in patients with chronic orchialgia who have failed conservative treatment options. Failures in MDSC could be due to small diameter nerves (≤1mm) left behind on the arteries and veins in the cord based on previous studies. Our goal was to assess if hydrodissection (HD) of the spermatic cord after MDSC would decrease the number of residual nerve fibers on the preserved arteries and veins without compromising blood flow. Prospective blinded randomized control trial: bilateral MDSC was performed on 22 adult rats (44 cords). Hydrodissection of the spermatic cord was performed on one side of each rat (side randomized) using the ERBEJET2 (ERBE Inc, Altanta, GA). The contralateral cord (no hydrodissection) was the control for each animal. Blood flow through the vessels was monitored using a micro Doppler probe (Vascular Technology Inc, Nashua, NH). After completion of MDSC with or without HD, the animal was euthanized and a cross section of the residual cord sent to pathology (blinded to technique) for H&E staining and evaluation for small nerve (≤1mm) density and signs of structural damage. The cord where HD had been performed had a significantly lower total median residual nerve count of 5 (0-10), compared to 8 (2-12) on the non-HD side (P=0.007). No structural damage was seen in the vessels in the cord that had undergone HD (gross exam and histology). Blood flow had been maintained in the vessels when the ERBEJET2 was set to 87psi (based on separate dose titration study on 2 similar rats 4 MDSC). Hydrodissection of the spermatic cord at 87psi after MDSC significantly decreases residual nerve density without compromising vascular integrity in a rat model.

Ladbroke Grove Station (2): design, construction and monitoring of remedial works

London Underground Limited's Ladbroke Grove Station, constructed around 100 years ago, was displaying signs of structural damage. The brick platform walls appeared to have rotated outwards from the tracks and vertical cracks of up to 5 mm wide were visible. Investigation and monitoring works were undertaken and proposals were outlined for remedial works. A design and build contract was subsequently awarded for remedial works. The earlier remedial proposals were reconsidered at design in order to arrive at the optimum solution, resulting in the least disruption to passengers. This paper discusses how the final solution was derived, the construction works and the monitoring of their effectiveness.

Ultrastructural observations on the cellular response of carp, Cyprinus carpio L., to eggs of the blood fluke Sanguinicola inermis Plehn, 1905 (Trematoda: Sanguinicolidae)

Abstract. The cellular response, within the kidney of experimentally infected carp to the presence of eggs of the blood fluke Sanguinicola inermis has been investigated using transmission electron microscopy. Initially, 0–1‐wcck‐old eggs were surrounded by host eosinophils which degranulated and broke down adjaeent to the egg shell. Infiltration by neutrophils and monocytes occurred around 1–2‐week‐old eggs. Eggs at 2–3 weeks of age began to become encapsulated, although the first signs of structural damage appeared when the eggs were 5–6 weeks of age.